This project is focused on the temporal and spatial pattern of noise-induced hair cell loss, as well as, the molecular "triggers" for the hair cell loss. Previous work has shown that the size of the cochlea lesion continues to "grow" after the exposure, that the increased hair cells is related to apoptosis and that the apoptotic cells have Caspase-3 expressed. This project extends our preliminary work with noise exposures that are likely to cause metabolic damage in the cochlea (4 kHz OB @ 105 dB SPL for 4h) or noise exposures that will cause both metabolic and mechanical damage (150dB pe SPL impulse). The experiments are designed to elucidate the progression of hair cell loss after noise exposures, the prevalence of apoptosis as reflected in nuclear shrinking, as well as, the expression of Caspase-3. A second set of experiments, with the same noise exposures, examines the relevance of Caspase-8 or 9 as precursors to Caspase-3. Lastly, the third set of experiments will distinguish the temporal sequence of ROS response with respect to caspase activation (i.e. which takes place first). Collectively, these experiments will help better understand the molecular pathways involved in cell death and the results will serve as a rationale for future therapeutic intervention.